This invention relates to polyvalent melanoma cell vaccines comprised of allogeneic melanoma cell lines which contain high concentrations of antigens which are immunogenic in melanoma patients.
The concept of using vaccines to induce specific immunity against cancer has existed since the turn of the century, when cancer therapists were first attracted by the success of vaccines in inducing active immunity against infectious diseases. Cancer vaccines differ from vaccines against infectious diseases in that they are administered as therapy after the advent of disease, rather than prophylactically before the disease develops. The theory behind vaccines for cancer and infectious diseases is, however, similar. Both seek to stimulate the patient's own immune system to fight the disease through the introduction of killed whole organisms or cells, specific subcellular antigens, and non-pathologic strains of living organisms or tumor cells. Morton, Sem Oncol 1986; 13(2):180-185.
Early attempts to induce tumor regression in cancer patients by immunizing them with their own tumors or with those from other patients were not properly evaluated; they lacked suitable controls and immunologic studies to determine whether the patients had actually been successfully immunized. However, there are well-documented instances of vaccine-induced immunity against cancer in animal models and evidence for serologic and clinical responses in man to suggest that active specific immunotherapy can be developed as a modality of treatment for cancer. Active immunotherapy became a realistic strategy after it was demonstrated that the induction of DCH reactions in certain malignant neoplasms, such as those induced by the intralesional injection of BCG (an attenuated strain of Mycobacterium) resulted in the regression and eradication of the directly injected cutaneous melanoma metastases and occasionally also in the regression of uninjected metastases. These reports rekindled interest in the century-old concept of a vaccine for cancer and revived efforts to find the crucial formulas for effective vaccine therapy.
Research efforts during the past twenty-five years have been primarily directed towards the development of more effective methods for the active specific immunotherapy of melanoma. Ann. Surg., pp 463-482 (October 1992), incorporated herein by reference. The conceptual basis for this focus has been based upon the original observation that the intratumoral injection of cutaneous metastases in melanoma patients with bacillus Calmette-Guerin (BCG) resulted in systemic enhancement of active immunity, producing rising titers of anti-melanoma antibodies and regression of other uninjected metastatic cutaneous lesions. See Morton et al., Surgery 1968; 64:233-240; Morton et al., Surgery 1970; 68:158-164. Biopsy of uninjected melanoma lesions that showed clinical regression demonstrated intense lymphocytic infiltration.
Limited success was experienced with the initial attempts to reproduce these observations by active immunotherapy with the intradermal or intralymphatic injection of a randomly selected tumor cell vaccine of unknown antigenicity, which was composed of irradiated allogeneic melanoma cells mixed with BCG. Morton et al., Aust NZ J Surg 1978; 48:49-52. This tumor cell vaccine will be referred to as "TCV" or "prior melanoma vaccine." It is now known that the melanoma cell lines selected for this TCV in the early active immunotherapy trials did not express an optimum quantity of melanoma-associated antigens (MAA). At that time MAA could not be quantitated in the vaccine and it was found that only 35% of immunized patients were high responders.
Thus a need exists for an effective vaccine capable of eliciting an immune reponse in melanoma patients.